The following discussion of the prior art was intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, however, reference to any prior art in this specification should be construed as an admission that such art was widely known or forms part of common general knowledge in the field.
“Vortioxetine” (also known as Lu AA21004) is chemically known as 1-{2-[(2,4-dimethylphenyl)sulfanyl]phenyl}piperazine of Formula (I), and as hydrobromide salt.

Vortioxetine is currently under development by Lundbeck and Takeda for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Regulatory approval for the treatment of MDD has been filed Europe and USA. It is a serotonine modulator and stimulator.
Vortioxetin was first disclosed specifically in U.S. Pat. No. 7,144,884 B2 and six alternative approaches to prepare compounds analogous to vortioxetine were provided.
U. S. PG-Pub. No. 2010/297240 A1 (The US '240 A1) discloses crystalline vortioxetine and various salts thereof. The US '240 A1, in addition, provides different polymorphic forms of vortioxetine hydrobromide—alpha, beta, gamma and hemihydrate forms and a mixture of ethyl acetate solvate and alpha form. The US '240 A1 also discloses seven alternative processes for preparation of vortioxetine. The US '240 A1 discloses that the compound 1,1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine as free base prepared in example 1(e) of WO 03/029232 A1 is in non-crystalline form.
U. S. PG-Pub. No. 2012/004409 A1 discloses a process for purification of vortioxetine hydrobromide salt and an isopropanol solvate thereof.
International (PCT) Publication No. WO 2013/102573 A1 also discloses a process for preparation of vortioxetine.
Crystalline solids normally require a significant amount of energy for dissolution due to their highly organized, lattice like structures. For example, the energy required for a drug molecule to escape from a crystal is more than from an amorphous or a non-crystalline form. It is known that the amorphous forms in a number of drugs exhibit different dissolution characteristics and in some cases different bioavailability patterns compared to the crystalline form (Econno T., Chem. Pharm. Bull., 1990; 38: 2003-2007). For some therapeutic indications, one bioavailability pattern may be favored over another. An amorphous form of rosuvastatin calcium, rabeprazole sodium are some of the examples of one amorphous drug exhibiting much higher bioavailability than the crystalline forms, which leads to the selection of the amorphous form as the final drug substance for pharmaceutical dosage from development. Additionally, the aqueous solubility of crystalline atorvastatin calcium is lower than its amorphous form, which may result in the difference in their in vivo bioavailability. Therefore, it is desirable to have amorphous forms of drugs with high purity to meet the needs of regulatory agencies and also highly reproducible processes for their preparation.
In view of the above, it is therefore, desirable to provide an efficient, more economical, less hazardous and eco-friendly process for the preparation of amorphous vortioxetine or salts thereof and hydrates thereof. The amorphous form provided herein is at least stable under ordinary stability conditions with respect to purity, storage and is free flowing powder.